A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss

A Phase 3 Study of Sodium Thiosulfate for Reduction of Cisplatin-Induced Ototoxicity in Children With Average-Risk Medulloblastoma and Reduced Therapy in Children With Medulloblastoma With Low-Risk Features

This phase III trial tests two hypotheses in patients with low-risk and average-risk medulloblastoma. Medulloblastoma is a type of cancer that occurs in the back of the brain. The term, risk, refers to the chance of the cancer coming back after treatment. Subjects with low-risk medulloblastoma typically have a lower chance of the cancer coming back than subjects with average-risk medulloblastoma. Although treatment for newly diagnosed average-risk and low-risk medulloblastoma is generally effective at treating the cancer, there are still concerns about the side effects of such treatment. Side effects or unintended health conditions that arise due to treatment include learning difficulties, hearing loss or other issues in performing daily activities. Standard therapy for newly diagnosed average-risk or low-risk medulloblastoma includes surgery, radiation therapy, and chemotherapy (including cisplatin). Cisplatin may cause hearing loss as a side effect. In the average-risk medulloblastoma patients, this trial tests whether the addition of sodium thiosulfate (STS) to standard of care chemotherapy and radiation therapy reduces hearing loss. Previous studies with STS have shown that it may help reduce or prevent hearing loss caused by cisplatin. In the low-risk medulloblastoma patients, the study tests whether a less intense therapy (reduced radiation) can provide the same benefits as the more intense therapy. The less intense therapy may cause fewer side effects. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. The overall goals of this study are to see if giving STS along with standard treatment (radiation therapy and chemotherapy) will reduce hearing loss in medulloblastoma patients and to compare the overall outcome of patients with medulloblastoma treated with STS to patients treated without STS on a previous study in order to make sure that survival and recurrence of tumor is not worsened.

Study Overview

• Status: Suspended
• Conditions: Medulloblastoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Drug: Cisplatin; Drug: Cyclophosphamide; Other: Survey Administration; Drug: Vincristine; Radiation: Radiation Therapy; Drug: Lomustine; Drug: Mesna; Drug: Sodium Thiosulfate

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of sodium thiosulfate (STS) infusion administered during cisplatin-containing chemotherapy cycles (compared to a historical cohort selected from ACNS0331 which received chemotherapy without STS) in reducing hearing loss in children with newly-diagnosed average-risk medulloblastoma.

II. To estimate and monitor event-free survival (EFS) in this study against a carefully selected cohort from ACNS0331 to guard against loss of efficacy due to STS.

SECONDARY OBJECTIVES:

I. To estimate and monitor overall survival (OS) in this study against a carefully selected control cohort from ACNS0331.

II. To estimate the incidence of ototoxicity-related cisplatin dose modifications in the average-risk cohort.

III. To estimate the incidence of cisplatin-related nephrotoxicity in both the average-risk and low-risk cohorts.

IV. To evaluate full scale intelligence neurocognitive outcomes and trajectories of patients with average-risk medulloblastoma treated with STS compared to the control cohort from ACNS0331.

V. To evaluate quality of life and psychosocial outcomes and trajectories of patients with average-risk medulloblastoma treated with STS compared to published norms.

VI. To estimate and monitor EFS and OS in patients with low-risk features treated using a reduced craniospinal radiation approach.

VII. To evaluate the trajectory of hearing loss in medulloblastoma patients treated with STS.

VIII. To evaluate household material hardship as a social determinant of neurocognitive, quality of life, and psychosocial outcomes in patients with average-risk and low risk medulloblastoma.

EXPLORATORY OBJECTIVES:

I. To obtain paired blood and tumor tissue to be banked for future biology studies involving comprehensive molecular analysis, including but not limited to whole exome sequencing, ribonucleic acid (RNA) sequencing, and methylation.

II. To bank blood and cerebrospinal fluid for future studies. III. To evaluate attention, processing speed, memory, and executive function neurocognitive outcomes and trajectories, as well as hearing-related quality of life outcomes and trajectories, of patients with average-risk medulloblastoma treated with STS.

IV. To evaluate neurocognitive, quality of life, and psychosocial outcomes of patients with low-risk features treated using a reduced craniospinal radiation approach.

OUTLINE:

CHEMORADIOTHERAPY: Patients undergo radiation therapy on weeks 1-7 and receive vincristine intravenously (IV) once weekly on weeks 2-7 in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning 4 weeks after chemoradiotherapy, patients receive lomustine orally (PO) on day 1 of cycles 1, 2, 4, 5, 7, and 8, cisplatin IV over 6 hours on day 1 of cycles 1, 2, 4, 5, 7, and 8, sodium thiosulfate IV over 15 minutes on day 1 of cycles 1, 2, 4, 5, 7, and 8, and cyclophosphamide IV over 30-60 minutes on days 1 and 2 of cycles 3, 6, and 9. Patients also receive vincristine IV on days 1, 8, and 15 of cycles 1, 2, 4, 5, 7, and 8, and on days 1 and 8 of cycles 3, 6, and 9. Treatment repeats every 6 weeks (cycles 1, 2, 4, 5, 7 and 8) or every 4 weeks (cycles 3, 6, and 9) for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for years 1-2, every 6 months for years 3-4, and then annually for years 5-10.

• Study Type: Interventional
• Enrollment (Estimated): 225
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202-3591
      • Arkansas Children's Hospital
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Long Beach, California, United States, 90806
      • Miller Children's and Women's Hospital Long Beach
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Madera, California, United States, 93636
      • Valley Children's Hospital
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
    • San Diego, California, United States, 92123
      • Rady Children's Hospital - San Diego
    • San Francisco, California, United States, 94158
      • UCSF Medical Center-Mission Bay
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I duPont Hospital for Children
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic-Jacksonville
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C S Mott Children's Hospital
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Children's Hospital-Royal Oak
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota - Minneapolis
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospitals and Clinics
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Saint Peter's University Hospital
    • Paterson, New Jersey, United States, 07503
      • Saint Joseph's Regional Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New Hyde Park, New York, United States, 11040
      • The Steven and Alexandra Cohen Children's Medical Center of New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Children's Hospital Medical Center of Akron
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Childrens Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404
      • Dayton Children's Hospital
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Richland Hospital
    • Greenville, South Carolina, United States, 29605
      • BI-LO Charities Children's Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • El Paso, Texas, United States, 79905
      • El Paso Children's Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78207
      • Children's Hospital of San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
    • Tacoma, Washington, United States, 98405
      • Mary Bridge Children's Hospital and Health Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• PRE-ENROLLMENT: Patients must be greater than or equal to 3 years and less than 22 years of age at the time of enrollment on Step 0

• PRE-ENROLLMENT: Patient is suspected to have newly-diagnosed medulloblastoma by institutional diagnosis

  • Please note: Patients with a pending result of cerebrospinal Fluid (CSF) cytology tests are eligible for enrollment on NCI-2014-02057 (APEC14B1) and the Medulloblastoma Pre Enrollment Eligibility Screening (Step 0)
• PRE-ENROLLMENT: Patient and/or their parents or legal guardians have signed informed consent for APEC14B1 Part A - Eligibility Screening and Molecular Characterization
• PRE-ENROLLMENT: The required specimens are projected to be submitted through APEC14B1 as soon as possible (ASAP), preferably within 5 days of definitive surgery

• PRE-ENROLLMENT: All patients must have rapid central pathology review on APEC14B1 prior to study enrollment on ACNS2031 step 1 in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031.

  • Note: Patients with a pending result of CSF cytology tests are eligible for the rapid central pathology screening review. Confirmation of CSF negativity is needed for enrollment on the ACNS2031 protocol.
• PRE-ENROLLMENT: All patients must have rapid central molecular screening review on APEC14B1 prior to study enrollment on ACNS2031 step 1, in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031

• PRE-ENROLLMENT: All patients who have pathology confirmed must have rapid central imaging screening review on APEC14B1 prior to study enrollment on ACNS2031 step 1

  • Note: Patients must not have metastatic disease on cranial or spinal MRI. Patients with > 1.5 cm^2 residual tumor after initial surgical resection may undergo a second surgical resection prior to subsequent therapy to render them eligible for this study. The day of the second resection to remove residual tumor will be regarded as the day of definitive surgery (Day 0) and must be within a month (31 days) of the initial resection
• PRE-ENROLLMENT: All patients who have pathology confirmed must have rapid central audiology review on APEC14B1 prior to study enrollment on ACNS2031 step 1
• Patients must be >= 4 years and =< 21 years of age at the time of enrollment
• Patients must be newly diagnosed and have eligibility confirmed by rapid central pathology and molecular screening reviews performed on APEC14B1 and via the Molecular Characterization Initiative

• Average-risk cohort

  • Clinico-pathologic criteria:

    • M0 disease
    • No diffuse anaplastic histology AND

  • Molecular criteria:

    • SHH, p53wt, GLI2 normal, MYCN normal, no chromosome 14q loss
    • Group 3, MYC normal, no isochromosome 17q
    • Group 4, no chromosome 11 loss

• Low-risk features cohort

  • Clinico-pathologic criteria:

    • M0 disease
    • No diffuse anaplastic histology AND

  • Molecular criteria:

    • Group 4, chromosome 11 loss

• Patients must have negative lumbar CSF cytology

  • Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF. Ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study. Patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status. Patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively
• Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1. Patients must have =< 1.5 cm^2 cross-sectional area of residual tumor. Whole brain MRI with and without gadolinium and spine MRI with gadolinium must be performed
• Patients must weigh > 10 kg
• Patients must be enrolled, and protocol therapy must be projected to begin, no later than 31 days after definitive diagnostic surgery (day 0)
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell count [RBC] transfusions) (within 7 days prior to enrollment)

• A serum creatinine (within 7 days prior to enrollment) based on age/gender as follows:

  • 4 to < 6 years (age); 0.8 mg/dL (male) 0.8 mg/dL (female)
  • 6 to < 10 years (age); 1 mg/dL (male) 1 mg/dL (female)
  • 10 to < 13 years (age); 1.2 mg/dL (male) 1.2 mg/dL (female)
  • 13 to < 16 years (age); 1.5 mg/dL (male) 1.4 mg/dL (female)
  • >= 16 years (age); 1.7 mg/dL (male) 1.4 mg/dL (female) OR a 24 hour urine Creatinine clearance >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
  • Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)

• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment)

  • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L

• Central nervous system function defined as:

  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
  • Patients must not be in status epilepticus, a coma or assisted ventilation at the time of study enrollment

• Auditory function defined as:

  • Patients must have normal hearing (defined as International Society of Pediatric Oncology [SIOP] grade 0) in at least one ear confirmed by rapid central audiology review performed on APEC14B1 prior to enrollment
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Patients with metastatic disease by either magnetic resonance imaging (MRI) evaluation or lumbar CSF cytology are not eligible. Patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
• Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids
• Patients must not have any known hypersensitivity to STS, sulfates/sulfites, or other thiol agents (e.g., amifostine, n-acetylcysteine, MESNA, and captopril)

• Pregnancy and Breastfeeding:

  • Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (chemoradiotherapy, maintenance); CHEMORADIOTHERAPY: Patients undergo radiation therapy on weeks 1-7 and receive vincristine IV once weekly on weeks 2-7 in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning 4 weeks after chemoradiotherapy, patients receive lomustine PO on day 1 of cycles 1, 2, 4, 5, 7, and 8, cisplatin IV over 6 hours on day 1 of cycles 1, 2, 4, 5, 7, and 8, sodium thiosulfate IV over 15 minutes on day 1 of cycles 1, 2, 4, 5, 7, and 8, cyclophosphamide IV over 30-60 minutes on days 1 and 2 of cycles 3, 6, and 9, and mesna IV over 15-30 minutes TID on days 1 and 2 of cycles 3, 6, and 9. Patients also receive vincristine IV on days 1, 8, and 15 of cycles 1, 2, 4, 5, 7, and 8, and on days 1 and 8 of cycles 3, 6, and 9. Treatment repeats every 6 weeks (cycles 1, 2, 4, 5, 7 and 8) or every 4 weeks (cycles 3, 6, and 9) for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Asta B 518; B-518; WR-138719; Other: Survey Administration; Ancillary studies; Drug: Vincristine; Given IV; Other Names: VCR; Leurocristine; Vincrystine; LCR; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Drug: Lomustine; Given PO; Other Names: CCNU; CeeNU; Gleostine; 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea; 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-; Belustin; Belustine; Cecenu; Chloroethylcyclohexylnitrosourea; Citostal; Lomeblastin; Lomustinum; Lucostin; Lucostine; N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea; Prava; RB-1509; WR-139017; Drug: Mesna; Given IV; Other Names: Mesnex; 2-Mercaptoethanesulfonate, Sodium Salt; Ausobronc; D-7093; Filesna; Mercaptoethane Sulfonate; Mercaptoethanesulfonate; Mesnil; Mesnum; Mexan; Mistabron; Mistabronco; Mitexan; Mucofluid; Mucolene; UCB 3983; Uromitexan; Ziken; Drug: Sodium Thiosulfate; Given IV; Other Names: Cyanide Antidote Package; Disodium Thiosulfate; S-Hydril; Sodium Hyposulfate; Sodium Thiosulfate Pentahydrate; Sodium Thiosulphate; Sodothiol; Thiosulfate, Sodium, Pentahydrate; Thiosulfuric Acid Disodium Salt

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	Will estimate the EFS distribution using Kaplan-Meier method.	From initiation of the protocol treatment to the occurrence of disease progression, disease recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 10 years
Percentage of patients with >= grade 2 hearing loss	Will estimate the number and percentage of patients with >= Grade 2 hearing loss using the society of pediatric oncology (SIOP) scale (defined as hearing threshold >20 dB at >= 4kHz) 4 weeks after the last dose of cisplatin. If hearing loss is observed in both ears, the worse ear will be used for this primary analysis. Will compare the observed rate of hearing loss in ACNS2031 (this trial) with the rate from the ACNS0331 historical cohort described above using 2-sample 1-sided t-test where a p value < 0.05 will lead to a significant result. Will also report the percentage of patients with >= grade 2 hearing loss in the better ear at 4 weeks after the last dose of cisplatin in ACNS2031 and will compare it with the rate from ACNS0331 historical cohort using Fisher's exact test.	At 4 weeks after the last dose of cisplatin

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Will calculate the OS distribution using Kaplan Meier method.	Up to 10 years
Incidence of ototoxicity-related cisplatin dose modifications in the average-risk cohort	Will be calculated by dividing the total number of ototoxicity-related cisplatin dose modifications by the cumulative dose of cisplatin. Summary statistics including mean, standard deviation (SD), median and range will be used to summarize the data by cohorts.	Up to 10 years
Full scale intelligence neurocognitive outcomes and trajectories of patients with average-risk medulloblastoma treated with sodium thiosulfate (STS)	Will be compared to the control cohort from ACNS0331. A psychologist-administered battery will be used to assess longitudinal trajectories in the estimated full scale intelligence quotient (FSIQ) using the Wechsler Intelligence Scale Vocabulary and Block Design subtest. Box-plots will be drawn for each time point to visually look for change over time. Will estimate pairwise changes in FSIQ between 9 month and 30-month and between 9-month and 60-month measurements. Summary statistics will be provided for each time point and for each pairwise change including mean, standard deviation, median and range. Will compare FSIQ between two time points using parametric or non-parametric one-sample approaches depending on the normality of the data.	Up to 5 years
Quality of life and psychosocial outcomes of patients with average-risk medulloblastoma treated with STS	Will compare quality of life (general) and psychosocial (adaptive, social, emotional, behavioral) outcomes from this study between baseline and post treatment as well as to the published healthy norms.	Up to 5 years
EFS in patients with low-risk features treated using a reduced craniospinal radiation approach	KM estimates of the EFS distributions for the low-risk cohort will be provided.	Up to 10 years
OS in patients with low-risk features treated using a reduced craniospinal radiation approach	KM estimates of the OS distributions for the low-risk cohort will be provided.	Up to 10 years
Household material hardship as a social determinant of neurocognitive, quality of life, and psychosocial outcomes in patients with average-risk and low-risk medulloblastoma	The Household Survey will be administered to parents at various timepoints to measure household material hardship. Summary statistics will be provided for each time point including mean, standard deviation, median and range for each outcome measure of interest.	Up to 60 months post-enrollment
Incidence of cisplatin-related nephrotoxicity in both the average-risk and low-risk cohorts	The frequency of cisplatin-related nephrotoxicity including Grade 3 and higher creatinine increase, acute kidney injury, and chronic kidney disease will be calculated per patient as raw counts. Summary statistics will be reported including mean, median, standard deviation and range by cohorts.	Up to 10 years
Trajectory of hearing loss medulloblastoma patients treated with STS	The number of patients with >= Grade 2 hearing loss using the SIOP scale in the evaluable ear at each time point will be summarized along with its 95% confidence interval.	Up to 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Paired blood and tumor tissue banking or future studies	Will obtain paired blood and tumor tissue to be banked for future biology studies involving comprehensive molecular analysis.	Up to 5 years
Blood and cerebrospinal fluid banking for future studies	Will bank blood and cerebrospinal fluid for future studies.	Up to 5 years
Hearing related-quality of life (HEAR-QL) of patients with average-risk medulloblastoma treated with STS	Hearing and Audiology Survey will examine parent and patient-perceived hearing loss, hearing aid use, and barriers to hearing aid use through descriptive statistics.	Up to 5 years
HEAR-QL of patients with low-risk features treated using a reduced craniospinal radiation approach	Hearing and Audiology Survey will examine parent and patient-perceived hearing loss, hearing aid use, and barriers to hearing aid use through descriptive statistics.	Up to 5 years
Attention, processing speed, memory, and executive function neurocognitive outcomes and trajectories of patients with average-risk medulloblastoma treated with STS		Up to 5 years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ralph Salloum, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Estimated): December 20, 2027
• Study Completion (Estimated): December 20, 2027

Study Registration Dates

• First Submitted: April 15, 2022
• First Submitted That Met QC Criteria: May 18, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Medulloblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Anti-Bacterial Agents; Antioxidants; Antitubercular Agents; Chelating Agents; Sequestering Agents; Cyclophosphamide; Cisplatin; Vincristine; Lomustine; Sodium thiosulfate; Mesna; Antidotes
• Other Study ID Numbers: ACNS2031 (Other Identifier: CTEP); U10CA180886 (U.S. NIH Grant/Contract); NCI-2022-04866 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes